Many nonpeptide C-2 symmetric and pseudosymmetric compounds have shown good biological activity as human immunodeficiency virus (HIV) protease inhibitors. Compounds and methods for their preparation are increasingly found in the literature. (Kempf et al., J. Org. Chem. 57, 5692-5700 (1992); Livermore et al., J. Med. Chem. 36, 3784-3794 (1993); Lam et al., Science 263, 380-384 (1994); Jadhav et al., WO 93/07128; EP 402,646; Dreyer et al., Biochemistry 32, 937-47 (1993); Sowin et al. WO 93/23361; Jadhav et al., Bioorganic & Med. Chem. Lett. 2, 353-356 (1992); Jadhav et al., U.S. Pat. No. 5,294,720.
U.S. Pat. No. 5,294,720 and European Patent Application 402,646 A1 describe the synthesis of diamine ##STR2## via coupling of aldehydes derived from suitably protected aminoacids.
Baker and Condon, J. Org. Chem. 1993, 58, 3277-3284, disclose a method for the preparation of linear diaminodiols from (-)-2,3-isopropylidene-D-threitol shown below. ##STR3##
European Patent Application 402,646 A1 also describes the synthesis of bisoxime (C) from the bisamide (B). This product was obtained in relatively poor yields and no further transformations were disclosed. ##STR4##
Lam et al., PCT International Publication Number WO 93/07,128 discloses cyclic carbonyl compounds and derivatives thereof which are useful as human immunodeficiency virus (HIV) protease inhibitors for the treatment of HIV infection. The compounds disclosed in WO 93/07128 include cyclic HIV protease inhibitor compounds of the formula below where W may be --N(R.sup.22)C(.dbd.O)N(R.sup.23)--. ##STR5##
The above methods for the preparation of linear diaminodiols use relatively expensive starting materials and toxic reagents.
The present invention provides a improved synthetic processes for the preparation of diamine intermediates useful for the synthesis of HIV protease inhibitors. The process of the present inventions uses inexpensive chiral raw materials and environmentally nonhazardous reagents.
None of the above-cited references describe the methods of the present invention for the synthesis of diamines useful as intermediates for the synthesis of HIV protease inhibitors.